PROJECT SUMMARY (See instructions); The Human Cancer Virology (VR) program is advancing understanding, prevention, and treatment of virus linked cancers and other cancers through fundamental and translational studies that encompass five of the seven well-established human tumor viruses. Program members are defining the mechanisms by which human tumor viruses replicate, maintain chronic infection, and promote tumor induction and maintenance; determining the progressive, genome-wide molecular changes in the development of virus-associated tumors; identifying viral and cellular biomarkers for improved tumor diagnosis, prognosis and treatment selection; and using their results to develop new approaches to prevent and treat tumor virus infection and oncogenesis. Program members' efforts have already changed UW-Madison clinical practices for hepatitis C virus treatment, are moving forward in testing new treatment approaches for papillomavirus-induced head/neck and cervical cancer, and have established strong foundations for similarly novel control strategies for cancers induced by Epstein-Barr virus and other viruses. To achieve their goals, program members collaborate extensively intra- and inter-programmatically, and integrate novel, synergistic approaches using cell culture, mouse models based on transgenes and patient explants, and large collections of relevant human tumor samples. The twelve program members include three practicing physician-scientists (two M.D.s and one M.D./Ph.D.) and nine Ph.D.s who collectively comprise a highly productive, interactive, diverse, and critical mass of expertise across the full spectrum of tumor virology from molecular biology to clinical studies. They represent six departments (Oncology, Medical Microbiology and Immunology, Medicine, Molecular Virology, Plant Pathology) in four Schools (School of Medicine and Public Health, Graduate School, College of Engineering, College of Agriculture and Life Sciences), plus two private biomedical research institutes (Howard Hughes Medical Institute and Morgridge Institute for Research). They have $3.8M/yr funding from NCI and $2.7M in other peer-reviewed funding. From 2007-2011 they had 133 cancer-relevant publications, which were overall 6% intra-programmatic and 15% inter-programmatic. For 2011, intra-programmatic publications advanced to 12% and inter-programmatic publications to 25%. This increase in collaborative publications reflects a steadily increasing number of joint projects and grants within and beyond the program.